Mosaicism in Fragile X syndrome: A family case series

• Published in: Journal of intellectual disabilities 2022-09, Vol.26 (3), p.800-807
• Main Authors: Saldarriaga, Wilmar, González-Teshima, Laura Yuriko, Forero-Forero, Jose Vicente, Tang, Hiu-Tung, Tassone, Flora
• Format: Article
• Language: English
• Subjects: Autism; Deoxyribonucleic acid; Diagnostic tests; DNA; Foreign Countries; Fragile X syndrome; Genetic Disorders; Genotype & phenotype; Heredity; Intellectual disabilities; Intellectual Disability; Males; Medical diagnosis; Mutation; Symptoms (Individual Disorders); Women
• ISSN: 1744-6295; 1744-6309
• DOI: 10.1177/1744629521995346

Fragile X syndrome (FXS) has a classic phenotype, however its expression can be variable among full mutation males. This is secondary to variable methylation mosaicisms and the number of CGG triplet repeats in the non-coding region of the Fragile X Mental Retardation 1 (FMR1) gene, producing a variable expression of the Fragile X Mental Retardation Protein (FMRP). Here we report a family with several individuals affected by FXS: a boy with a hypermethylated FMR1 mutation and a classic phenotype; a man with an FMR1 gene mosaicism in the range of premutation (PM) and full mutation (FM), who has a mild phenotype due to which FXS was initially disregarded; and the cases of four women with a FM and mosaicism. This report highlights the importance of DNA molecular testing for the diagnosis of FXS in patients with developmental delay, intellectual disability and/or autism due to the variable phenotype that occurs in individuals with FMR1 mosaicisms.